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Cell injury, adaptation and death
Unite one
Lab.
A basic cell is bounded by a cell membrane. Within the cell is a nucleus containing
chromatin, often condensed at the periphery, along with larger clumps called
chromocenters, and in some cells a nucleolus into which RNA is concentrated. The
cytoplasm contains the cytosol and a variety of organelles, including mitochondria that
power the cell via production of ATP, endoplasmic reticulum and ribosomes that
synthesize new materials, a Golgi apparatus, and lysosomes.
Cellular structure and function are determined by various cellular components. Glandular epithelial
cells, such as the lining of the small intestine with a brush border, have microvilli. Glandular epithelial
cells may have cytoplasmic mucin vacuoles. Epithelial cells are characterized by the presence
of desmosomes that connect them. Many types of cells have cytoskeletal proteins. Squamous epithelial
cells may have cytoskeletal elements such as tonofilaments. Cells with neuroendocrine differentiation
tend to be rounded and may have cytoplasmicneurosecretory granules.The extracellular matrix
(ECM) is composed of a variety of components. An adhesion complex in the cell links to integrin that
extends outward. Seen here is a basement membrane. An important component of basement
membrane is laminin, which acts as a "lag bolt" to connect cells via integrin to the ECM. Collagen
(type IV in basement membrane and types V and VI as fine fibrils) comprises the structural component
of ECM that provides shape and stability. Fibronectin is an adhesive protein that acts as a "glue" to
hold the various components together.
There are some muscle fibers here that show atrophy.
The number of cells is the same as before the atrophy occurred, but
the size of some fibers is reduced. This is a response to injury by
"downsizing" to conserve the cell. In this case, innervation of the
small fibers in the center was lost. This is a trichrome stain.
The testis at the right has
undergone atrophy and is much
smaller than the normal testis at
the left.
This is cerebral atrophy in a
patient with Alzheimer
disease. The gyri are
narrowed and the intervening
sulci widened, particularly
pronounced toward the
frontal lobe region.
Here is the centrilobular portion of liver next to a central vein.
The cells have reduced in size or been lost from hypoxia.
The pale brown-yellow pigment is lipochrome that has accumulated
as the atrophic and dying cells undergo autophagocytosis.
This is cardiac hypertrophy involving the left ventricle. The
number of myocardial fibers does not increase, but their size can
increase in response to an increased workload, leading to the
marked thickening of the left ventricle in this patient with systemic
hypertension.
The prominent folds of endometrium in this uterus opened to
reveal the endometrial cavity are an example of hyperplasia. Cells
forming both the endometrial glands and the stroma have increased
in number. As a result, the size of the endometrium has increased.
This increase is physiologic with a normal menstrual cycle.
This is an example of prostatic hyperplasia. The normal adult male
prostate is about 3 to 4 cm in diameter. The number of prostatic
glands, as well as the stroma, has increased in this enlarged prostate
seen in cross section. The pattern of increase here is not uniform, but
nodular. This increase is in response to hormonal manipulation, but
in this case is not a normal physiologic process.
Here is one of the nodules of hyperplastic prostate, with many
glands along with some intervening stroma. The cells making up
the glands are normal in appearance, but there are just too many
of them.
Metaplasia of laryngeal respiratory epithelium has occurred here
in a smoker. The chronic irritation has led to an exchanging of
one type of epithelium for another. Metaplasia is not a normal
physiologic process and may be the first step toward neoplasia.
The normal respiratory epithelium
The more resilient squamous epithelium
Metaplasia of the normal esophageal squamous mucosahas
occurred here, with the appearance of gastric type columnar
mucosa.
This is dysplasia. The normal cervical squamous epitheliumhas
become transformed to a more disorderly growth pattern,
or dysplastic epithelium. This is farther down the road toward
neoplasia, but dysplasia is still a potentially reversible process.
When there
is marked
cellular
injury, there
is cell death.
This microscopic appearance of myocardium is a mess because so
many cells have died that the tissue is not recognizable. Many nuclei
have become pyknotic (shrunken and dark) and have then undergone
karorrhexis (fragmentation) and karyolysis (dissolution). The
cytoplasm and cell borders are not recognizable.
Here is myocardium in which the cells are dying. The nuclei of
the myocardial fibers are being lost. The cytoplasm is losing its
structure, because no well-defined cross-striations are seen.
is a more orderly process of cell death in which there Apoptosis
is individual cell necrosis, not necrosis of large numbers of cells.
In this example, liver cells are dying individually (arrows) from
injury by viral hepatitis. The cells are pink and without nuclei.
Individual cells fragment and are consumed by phagocytes to give
the appearance of clear spaces filled with cellular debris.
Apoptosis is controlled by many mechanisms.
Genes such as Bcl-2 are turned off and Bax genes turned on.
Proteolytic enzymes called caspases produce much cellular
breakdown.
In this fetal
there is thymus
involution of
thymic
lymphocytes by
the mechanism
of apoptosis.
This is an example of coagulative necrosis.
This is the typical pattern with ischemia and infarction (loss
of blood supply and resultant tissue anoxia).
Here, there is a wedge-shaped pale area of coagulative
necrosis (infarction) in the renal cortex of the kidney.
When many cells undergo
necrosis at once, then
definable patterns of
necrosis are produced,
depending upon the nature
of the injury, the type of
tissue, and the length of
time.
Microscopically, the renal cortex has undergone anoxic injury at the
left so that the cells appear pale and ghost-like. There is a
hemorrhagic zone in the middle where the cells are dying or have not
quite died, and then normal renal parenchyma at the far right. This is
an example of coagulative necrosis.
The contrast
between normal
adrenal cortex
and the small
pale infarct is
good.
The area just under the capsule is spared because of blood
supply from capsular arterial branches.
This is an odd place for an infarct, but it illustrates the
shape and appearance of an ischemic (pale) infarct well.
Since the etiology of coagulative necrosis is usually
vascular with loss of blood supply, the infarct occurs in a
vascular distribution. Thus, infarcts are often wedge-
shaped with a base on the organ capsule.
Two large
infarctions
(areas of
coagulative
necrosis) are
seen in this
sectioned
spleen.
The small
intestine is
infarcted.
The dark red to grey infarcted bowel contrasts with the
pale pink normal bowel at the bottom.
Some organs such as bowel with anastomosing blood supplies, or liver with a dual
blood supply, are hard to infarct. This bowel was caught in a hernia and the
mesenteric blood supply was constricted by the small opening to the hernia sac.
To be continued